The hypothesis that neutrophil activation exacerbates brain injury in acute stroke is currently receiving wide acceptence. However, the temporal relationship of neutrophil activation to the ishemic event in clinical states is not clear. Therefore this study was undertaken to examine human neutrophil activation by technique of luminol-dependent chemiluminescence in both acute and bland hemorrhagic stroke. Patients (bland, n=18; hemorrhagic, n=16) were entered into this study within six hours of the ictus. These results were compared to other clinical central nervous system insults: subarachnoid hemorrage (n=11), spinal trauma (n=9) and isolated closed head injury (n=19). All subjects were sampled upon presentation to the emergency room and 0.5, 1, 2, 3, 4 and 5 days following the event. Neutrophil activation as determined by luminol-dependent chemiluminescence, was evident at days 1 and 2 following the ictus in the bland stroke group (p<0.05), although this trend was not demonstrated for hemorrhagic stroke. Patients suffering a closed head injury demonstrated a more delayed increase in neutrophil activation whereas no significant change was demonstrated for the groups with spinal trauma or subarachnoid hemorrhage. These results support a role for neutrophil activation during various central nervous system insults and provide a temporal framework for considering drug therapy directed at transient suppression of neutrophil function. Data were analyzed using the CDMAS resource.